1. Field of the Invention
The present invention relates to a method for the treatment of gallstones, and more particularly to a method involving the perfusion of a solvent adjacent the gallstones.
2. Description of the Prior Art
Gallstones occur in a significant number of persons, with obesity and pregnancy being among the known predisposing factors. The causes of the formation of gallstones, more particularly known as biliary calculi, are generally obscure, with biliary stasis and disrupted cholesterol metabolism having been suggested as possible causative factors. Gallstones generally are found in the gallbladder, a condition known as cholelithiasis, or in the common duct, a condition known as choledocholithiasis. Gallstones are generally of three types, pure pigment stones of calcium bilirubinate which occur in hemolytic diseases, cholesterol stones, and mixed stones, the latter two types accounting for 80% of stone occurences.
Patients having gallstones may be completely asymptomatic for long periods. However, gallstones are generally accompanied by biliary colic, frequently with jaundice. Nausea and vomiting may also exist, and frequently the patient experiences regional pain and tenderness, as well as upper abdominal discomfort.
The treatment for gallstones in the past has followed two general courses. Immediate relief of the pain and discomfort associated with gallstones is generally attempted through the use of antispasmodics, such as amyl nitrite, nitroglycerin or atropine. Analgesics, such as meperidine, which also has some antispasmodic action, or stronger medicines in the case of more severe pain, may also be necessary. Typically, a low-fat high-protein, high-carbohydrate diet is recommended to lessen the likelihood of repeated attacks and to reduce the operative risk in subsequent surgery.
The potential for developing acute cholecystitis and its complications has generally meant in the past that surgery, known as cholecystectomy (removal of the gallbladder), would be required. Mortality associated with this operative technique is low, although the mortality rate is high due to resultant complications, particularly in poor-risk patients. Alternatively, surgical procedures may include mechanical stone extraction through the T-tube tract or retrograde endoscopic sphincterotomy, but these approaches may be contraindicated or unsuccessful.
A number of solvents have been proposed in the prior art for the dissolution of gallstones by the process of infusion or perfusion. Organic solvents such as ether, chloroform and d-limonene have been used, but these solvents are poorly tolerated by patients and are potentially toxic without highly favorable results. Oxycholic acid and sodium cholate in 100-200 mM solutions have shown definite but low solubilizing capacities for gallstones. Uncontrolled studies with these compounds have reported disappearance of distal common bile duct stones in 1-4 weeks, but often with bile acid diarrhea. Kenodeoxycholic acid has been found to be more preferable, but also is relatively slow and may result in problems with repeated use. The use of heparin in saline solution has also been found to function poorly to fragment or dissolve gallstones.
Prior art studies directed at controlling the level of cholesterol in blood serum have noted the solubility of cholesterol in the short chain fatty acids and their esters. A number of patents have issued relating to compositions or methods directed toward reducing the cholesterol level in blood serum by administration of acid or ester compounds, as exemplified by U.S. Pat. No. 3,495,011, issued to Fossel on Feb. 10, 1970, and U.S. Pat. No. 3,158,541, issued to Sutherland on Nov. 24, 1964. Each of the prior art disclosures of this type, however, are concerned with compounds, typically administered orally, for the general reduction of the cholesterol level in the blood.
In an article entitled "Solubility of Cholesterol in Various Fats and Oils", authored by David Kritchevsky and Shirley A. Tepper of the Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania, the results of solubility tests for cholesterol in medium chain triglycerides are recited. This article was concerned with the effect of fatty acid diets on serum cholesterol levels, and concluded that solubility measurements in vitro do not correlate with the effects of the various fats on serum cholesterol levels.